Bone marrow-derived mesenchymal stem cells transplantation attenuates renal fibrosis following acute kidney injury by repairing the peritubular capillaries

Sepsis is a common risk factor for acute kidney injury (AKI). Bone marrow-derived mesenchymal stem cells (BMSCs) bear multi-directional differentiation potential. This study explored the role of BMSCs in sepsis-induced AKI (SI-AKI). A rat model of SI-AKI was established through cecal ligation and perforation. The SI-AKI rats were injected with CM-DiL-labeled BMSCs, followed by evaluation of pathological injury of kidney tissues and kidney injury-related indicators and inflammatory factors. HK-2 cells were treated with lipopolysaccharide (LPS) to establish SI-SKI model in vitro. Levels of mitochondrial proteins, autophagy-related proteins, NLRP3 inflammasome-related protein, and expressions of Parkin and SIRT1 in renal tubular epithelial cells (RTECs) of kidney tissues and HK-2 cells were detected. The results showed that BMSCs could reach rat kidney tissues and alleviate pathological injury of SI-SKI rats. BMSCs inhibited inflammation and promoted mitophagy of RTECs and HK-2 cells in rats with SI-AKI. BMSCs upregulated expressions of Parkin and SIRT1 in HK-2 cells. Parkin silencing or SIRT1 inhibitor reversed the promoting effect of BMSCs on mitophagy. BMSCs inhibited apoptosis and pyroptosis of RTECs in kidney tissues by upregulating SIRT1/Parkin. In conclusion, BMSCs promoted mitophagy and inhibited apoptosis and pyroptosis of RTECs in kidney tissues by upregulating SIRT1/Parkin, thereby ameliorating SI-AKI.

Download Full-text

Hypoxic Preconditioning with Cobalt of Bone Marrow Mesenchymal Stem Cells Improves Cell Migration and Enhances Therapy for Treatment of Ischemic Acute Kidney Injury

PLoS ONE ◽

10.1371/journal.pone.0062703 ◽

2013 ◽

Vol 8 (5) ◽

pp. e62703 ◽

Cited By ~ 53

Author(s):

Xiaofang Yu ◽

Chunlai Lu ◽

Hong Liu ◽

Shengxiang Rao ◽

Jieru Cai ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Acute Kidney Injury ◽

Mesenchymal Stem Cells ◽

Cell Migration ◽

Kidney Injury ◽

Hypoxic Preconditioning ◽

Marrow Mesenchymal Stem Cells ◽

Ischemic Acute Kidney Injury

Download Full-text

Bone marrow derived mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

10.21203/rs.3.rs-17590/v3 ◽

2020 ◽

Author(s):

song zhou ◽

Yu-ming Qiao ◽

Yong-guang Liu ◽

Ding Liu ◽

Jian-min Hu ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Acute Kidney Injury ◽

Mesenchymal Stem Cells ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Underlying Mechanism ◽

P53 Expression ◽

Inflammatory Microenvironment ◽

Apoptotic Effect

Abstract Background Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect; however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow derived mesenchymal stem cells (BMSCs) for AKI treatment. Results We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated SIRT1 and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did. Conclusions Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.

Download Full-text

Functional Recovery after Acute Kidney Injury in Mice Treated with a Combination of Matrigel and Bone Marrow-Derived Mesenchymal Stem Cells

Transplantation Journal ◽

10.1097/00007890-201211271-01140 ◽

2012 ◽

Vol 94 (10S) ◽

pp. 591

Author(s):

H.-S. Nam ◽

P. K. Teotia ◽

K.-M. Park ◽

K. E.-D. Hussein ◽

H.-H. Kwak ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Acute Kidney Injury ◽

Mesenchymal Stem Cells ◽

Functional Recovery ◽

Kidney Injury

Download Full-text

CXCR4-overexpressing bone marrow-derived mesenchymal stem cells improve repair of acute kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00178.2013 ◽

2013 ◽

Vol 305 (7) ◽

pp. F1064-F1073 ◽

Cited By ~ 49

Author(s):

Nanmei Liu ◽

Andreas Patzak ◽

Jinyuan Zhang

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Acute Kidney Injury ◽

Cell Death ◽

Mesenchymal Stem Cells ◽

Renal Function ◽

Caspase 3 ◽

Kidney Injury ◽

Nuclear Antigen ◽

Tubular Cells

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) can repair acute kidney injury (AKI), but with limited effect. We test the hypothesis that CXCR4 overexpression improves the repair ability of BMSCs and that this is related to increased homing of BMSCs and increased release of cytokines. Hypoxia/reoxygenation-pretreated renal tubular epithelial cells (HR-RTECs) were used. BMSCs, null-BMSCs, and CXCR4-BMSCs were cocultured with HR-RTECs. The number of migrating BMSCs was counted. Proliferating cell nuclear antigen (PCNA) expression, cell death, and expressions of cleaved caspase-3 and Bcl-2 in cocultured HR-RTECs were measured. Cytokeratin 18 (CK18) expression and cytokine secretions of the BMSCs cultured with HR-RTEC supernatant were detected. BMSC homing, renal function, proliferation, and cell death of tubular cells were assayed in the AKI mouse model. CXCR4-BMSCs showed a remarkable expression of CXCR4. Stromal cell-derived factor-1 in the HR-RTEC supernatant was increased. Migration of BMSCs was CXCR4-dependent. Proportions of CK18+ cells in BMSCs, null-BMSCs, and CXCR4-BMSCs showed no difference. However, CXCR4 overexpression in BMSCs stimulated secretion of bone morphogenetic protein-7, hepatocyte growth factor, and interleukin 10. The neutralizing anti-CXCR4 antibody AMD3100 abolished this. In cocultured HR-RTECs the proportions of PCNA+ cells and Bcl-2 expression were enhanced; however, the proportion of annexin V+ cells and expression of cleaved caspase-3 were reduced. The in vivo study showed increased homing of CXCR4-BMSCs in kidneys, which was associated with improved renal function, reduced acute tubular necrosis scoring, accelerated mitogenic response of tubular cells, and reduced tubular cell death. The enhanced homing and paracrine actions of BMSCs with CXCR4 overexpression suggest beneficial effects of such cells in BMSC-based therapy for AKI.

Download Full-text